We have previously shown that anti-Ig heavy chain-specific antibodies, when injected into mice from birth onward, can achieve severe multi-class or class-specific immunosuppression of normal B cells. We have also shown that these antibodies, first administered at birth or in adulthood, can prevent the growth of certain murine malignant lymphoid cells, particularly those of plasmacytomas. We have recently established the Fc-dependence of such suppression for normal B cells and used this observation to base a working model for the mode of action involved. I will now continue our study of heavy chain isotype suppression for the dual purposes of refining our model which explains the mechanism of this phenomenon and of developing applied models for the study of several disease processes of great clinical significance. Refinements of the mechanistic model will center around determination of: 1) the manner in which surface Ig-binding and Fc attachment by anti-Ig interact to generate a direct inhibitory immune signal (by studying the blocking capacity of F(ab')2 fragments), 2) the possible participation of suppressor cells (by adoptively transferring cells from suppressed mice), 3) the role of lymphocyte surface IgD (by using anti-delta antibodies), 4) the nature of surface determinants of suppressed cells (by flow cytometry), and 5) the nature of lymphoid changes accompanying adult-initiated anti-Ig treatment (by morphological and histological examination). The focus of applied model development will now be narrowed from the three previous cases of helminth expulsion, IgE suppression, and malignant lymphoid cell inhibition to a concentrated effort on plasmacytoma control. Emphasis here will be on 1) comparison of the mechanism of isotype suppression of normal as opposed to malignant cells (by using phylogenetically diverse antibodies and F(ab')2 fragments), 2) determination of the need for free anti-Ig antibodies (by transferring potential "armed" effector cells), and 3) discrimination of isotypic vs. idiotypic effects (by studying anti-Ig effects on non-homologous plasmacytomas).